Research Interests

B cell differentiation is a highly regulated process. At every step of B cell activation and maturation, mechanisms exist for eliminating or inhibiting autoreactive clones. Deficient control of autoreactive B cells has been implicated in the development and maintenance of several autoimmune diseases. My work focuses on the different mechanisms controlling selection and survival of germinal centre B cells and plasma cells.

1- Survival and homeostasis of plasma cells in the bone marrow depend on soluble factors provided by the microenvironment. The control of long-lived plasma cell survival is a critical goal for the treatment of autoimmune diseases characterized by the production of auto-antibodies. I have recently showed that in lupus nephritis, autoreactive plasma cells mostly home and survive in the inflamed kidneys, suggesting that the renal plasma cell niche may constitute a new therapeutic target. The identification of this cellular niche is in progress.

2- The germinal centre reaction is crucial for the development of switched and high-affinity plasma cells and memory B cells following T-dependent immunisation. Potentially autoreactive clones might also be generated or expanded during the germinal centre reaction and need to be counter-selected. Using a knock-in mouse system where the FcgammaRIIb promoter from wild mice was introduced in a C57BL6 background, I have demonstrated that natural variants of FcgammaRIIb control the up-regulation of this inhibitory receptor upon B cell activation. Accordingly, these knock-in mice failed to up-regulate FcgammaRIIb on germinal centre B cells. Using this model, we were able to demonstrate that FcgammaRIIb up-regulation on germinal centre B cells constitutes an important mechanism controlling the counter-selection of autoreactive B cell clones and the affinity maturation.

Kidneys from old autoimmune prone mice have been stained for laminin (red) to highlight the tubular organisation and for IgG (green). Immune complex deposition in the glomeruli and infiltrating plasma cells in the tubuloinsterstitium can be observed.

Spleen from mice immunized with NP-KLH in alum for 11 days have been stained with an anti-IgD (blue), an anti-KI67 (red) and with TUNEL (green). The B cell follicle is stained with the anti-IgD whereas the germinal centre B cells are positive for the cell cycle marker KI67. B cell clones which are counter-selected in the germinal centre are dying by apoptosis and are positive for the TUNEL staining.

Spleen from mice immunized with NP-KLH in alum for 11 days have been stained with an anti-IgD (blue), an anti-KI67 (green) and with NP-PE (red). The B cell follicle is stained with the anti-IgD whereas the germinal centre B cells are positive for the cell cycle marker KI67. Antigen-specific germinal centre B cells are both green and red.

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